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为探讨构效关系,合成了1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其喹啉、萘啶、吡啶[2,3-C]哒嗪环系类似物16个。测定了对大肠杆菌的MIC。用Hückel分子轨道理论(HMO)方法计算了四个母体环上电子密度。结果表明:环中氮的位置对药效团——3位羧基和4位羰基氧原子上电子密度的影响较大而影响其抗菌活性。喹啉、萘啶两环系的3位羧基和4位羰基氧原子上的电子密度较高,其体外抗菌活性较高;而噌啉及吡啶[2,3-C]哒嗪两环系的电子密度较低,其体外抗菌活性较低甚至消失。
To explore the structure-activity relationship, 1-p-fluorophenyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazine) cinnoline-3-carboxylic acid and its quinoline were synthesized. 16 naphthyridine and pyridine [2,3-C] pyridazine ring analogues. The MIC against Escherichia coli was determined. The electron density of the four parent rings was calculated using the Hückel theory of molecular orbital (HMO). The results showed that the position of nitrogen in the ring had a great effect on the electron density of the 3-position carboxyl group and 4-position carbonyl oxygen atom of the pharmacophore, which affected its antibacterial activity. Quinoline, naphthyridine two ring system 3 carboxyl and 4 carbon oxygen atoms on the higher electron density, high in vitro antibacterial activity; and cinnoline and pyridine [2,3-C] pyridazine two ring system Lower electron density, the antibacterial activity in vitro is low or even disappear.